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Low levels of progesterone and derivatives in cerebrospinal fluid of patients affected by status epilepticus
Author(s) -
Meletti Stefano,
Lucchi Chiara,
Monti Giulia,
Giovannini Giada,
Bedin Roberta,
Trenti Tommaso,
Rustichelli Cecilia,
Biagini Giuseppe
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14550
Subject(s) - allopregnanolone , neuroactive steroid , pregnanolone , pregnenolone , pregnenolone sulfate , medicine , cerebrospinal fluid , endocrinology , status epilepticus , gabaa receptor , epilepsy , hormone , receptor , psychiatry , steroid
Neurosteroids such as allopregnanolone may play a role in epilepsy as positive modulators of inhibitory currents mediated by γ‐aminobutyric acid type A ( GABA A ) receptor. Indeed, these molecules have been consistently shown to be anticonvulsants in animal models, but their role is still unclear in patients. For this reason, we investigated neurosteroids in the cerebrospinal fluid ( CSF ) of patients with status epilepticus ( SE ) by liquid chromatography tandem‐mass spectrometry. Patients were retrospectively identified within subjects who received a lumbar puncture in the 2007–2017 period. Seventy‐three patients (median age 65, ranging from 13 to 94 years; 67% women) with SE were evaluated. Controls ( n = 52, median age 53, ranging from 16 to 93 years; 65% women) were patients presenting with symptoms for which a lumbar puncture was required by clinical guidelines, and who were negative at the end of the diagnostic work‐up. Progesterone was 64% lower in patients with SE ( p < 0.001). With respect to progesterone, upstream pregnenolone sulfate and pregnenolone did not change. Instead, downstream 5α‐dihydroprogesterone, pregnanolone and allopregnanolone were, respectively, 49% ( p < 0.001), 21% ( p < 0.01) and 37% ( p < 0.001) lower than in controls. Duration or type of SE , age and sex did not consistently affect CSF neurosteroid levels in the SE cohort. Instead, pregnenolone sulfate (Spearman's ρ = 0.4335, p < 0.01), allopregnanolone (ρ = 0.4121, p < 0.05) and pregnanolone (ρ = 0.592, p < 0.001) levels significantly increased by aging in controls. We conclude that neurosteroidogenesis is defective in patients with SE .